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Biomedical subjects

T Tokura

Publications and source records attributed to T Tokura.

At least 19 recordsLinked to original sources
PubMed2001

Plasma levels of mature form of adrenomedullin in patients with haemodialysis.

BACKGROUND: Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide with hypotensive effects. Immunoreactive AM in human plasma consists of the biologically active mature form, AM (1-52)-CONH2 (mAM) and the intermediate form, AM-gly-COOH (iAM). However, the different effects of mAM and iAM in patients on haemodialysis (HD) have remained unclear. METHODS: Thirty-nine patients on HD and 10 controls were included in this study. We determined plasma levels of mAM and iAM using an immunoradiometric assay that recognizes total AM (tAM) and another that is specific for only mAM. RESULTS: The plasma concentrations of mAM and iAM in patients before HD were significantly higher than those in the controls (n=10) (4.76+/-0.28 vs 1.28+/-0.22 fmol/ml, P<0.001, 25.99+/-1.47 vs 8.52+/- 0.91 fmol/ml, P<0.001 respectively). The plasma levels of mAM and iAM before HD significantly and negatively correlated with systolic blood pressure (SBP) (r=-0.46, P<0.01, and r=-0.32, P<0.05 respectively) and diastolic blood pressure (DBP) (r=-0.32, P<0.05, and r=-0.35, P<0.05 respectively). After HD, plasma mAM and iAM levels as well as SBP and DBP were significantly lower than before HD. Plasma levels of mAM and iAM correlated significantly (r=0.73, P<0.001). CONCLUSIONS: These data suggest that mAM and/or iAM are involved in blood pressure regulation in patients undergoing HD, and further work is needed to understand the precise role of adrenomedullin in this regulation.

Adrenomedullin↗
PubMed2001

Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice.

The relationship between abnormal cell proliferation and aberrant control of hormonal secretion is a fundamental and poorly understood issue in endocrine cell neoplasia. Transgenic mice with parathyroid-targeted overexpression of the cyclin D1 oncogene, modeling a gene rearrangement found in human tumors, were created to determine whether a primary defect in this cell-cycle regulator can cause an abnormal relationship between serum calcium and parathyroid hormone response, as is typical of human primary hyperparathyroidism. We also sought to develop an animal model of hyperparathyroidism and to examine directly cyclin D1's role in parathyroid tumorigenesis. Parathyroid hormone gene regulatory region--cyclin D1 (PTH--cyclin D1) mice not only developed abnormal parathyroid cell proliferation, but also developed chronic biochemical hyperparathyroidism with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH. Thus, this animal model of human primary hyperparathyroidism provides direct experimental evidence that overexpression of the cyclin D1 oncogene can drive excessive parathyroid cell proliferation and that this proliferative defect need not occur solely as a downstream consequence of a defect in parathyroid hormone secretory control by serum calcium, as had been hypothesized. Instead, primary deregulation of cell-growth pathways can cause both the hypercellularity and abnormal control of hormonal secretion that are almost inevitably linked together in this common disorder.

Adenoma↗
PubMed2001

[Cholesterol embolism after percutaneous transluminal coronary angioplasty procedure: a case report].

A 68-year-old man with chest pain was treated under a diagnosis of angina pectoris based on coronary angiography by percutaneous transluminal coronary angioplasty including stent implantation performed by the femoral approach. About 1 month after intervention, his renal function deteriorated and purpura appeared on both feet, especially at the toe tips. He was treated under a tentative diagnosis of cholesterol embolism conservatively at the out-patient clinic. However, he was admitted by ambulance due to worsening renal failure 2 months later and died from multiple organ failure 2 weeks after admission. Autopsy examination identified cholesterol embolism due to crystal emboli in several organs. Cholesterol embolism rarely occurs after angiographic or interventional procedures, but is difficult to diagnose clinically and there is no established therapy. The number of intervention and angiography procedures is increasing, so the occurrence of embolism as a complication of these procedures might also increase.

Aged↗
PubMed1999

Plasma and urine levels of adrenomedullin and proadrenomedullin N-terminal 20 peptide in chronic glomerulonephritis.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide present in the precursor of adrenomedullin (AM), a vasodilative and natriuretic peptide. We examined the plasma and urinary levels of these peptides in patients with chronic glomerulonephritis (CGN). The mean plasma AM concentration of the patients with CGN did not differ from that of control subjects (4.17 +/- 0.17 v 3.87 +/- 0.21 fmol/mL, respectively), whereas urinary AM excretion was significantly less in the patients with CGN (5.96 +/- 0.95 v control, 8.93 +/- 1.02 fmol/mg of creatinine; P < 0.05). Plasma concentrations and urinary excretion of PAMP were significantly less for the patients with CGN compared with control subjects (0.91 +/- 0.08 v 1.23 +/- 0.20 fmol/mL; P < 0.05 and 25.0 +/- 3.0 v 35.0 +/- 3.6 fmol/mg of creatinine, respectively; P < 0. 05). The plasma AM concentration was negatively correlated with plasma renin activity (r = -0.58; P < 0.01) and aldosterone concentration (r = -0.40; P < 0.05). Urinary excretions of AM and PAMP showed significant correlations with urine excretion of sodium (r = 0.39; P < 0.05 and r = 0.49; P < 0.01, respectively). These findings suggest that AM and PAMP may have roles in the regulation of sodium in patients with CGN.

Adrenomedullin↗
PubMed1999

[Age-related changes in Bruch's membrane in rats].

PURPOSE: We investigated rats were worth the experimental animal on the aging changes in Bruch's membrane. METHODS: We did an ultramicromorphological study on the aging changes in Bruch's membrane, in male Sprauge-Dawley rats at 1,6,12 and 27 months after their birth. RESULTS: With the aging, the basement membranes on both sides of Bruch's membrane have become thick. At 6 months of age, the basement membranes of the endothelial cells of the choriocapillaris were found to be multilayered and cracked and pseudopodia of the endothelium were also observed toward the retinal pigment epithelium. At 12 months of age, we found vacuoles in the basal portion of the retinal pigment epithelium, as well as fibrillae and a part of the process of a cell in the outer collagenous zone correspond with the portion of the multilayered and cracked basement membranes of the endothelial cells of the choriocapillaris. At the age of 27 months, the basement membranes were thicker and a basal laminar deposit was seen. Prominent changes such as disappearance of the elastic fibers and increase of the collagenous fibers and fibrillae were also seen in some portions. CONCLUSIONS: Thus, the aging changes in Bruch's membrane of rats were remarkably reinforced in accordance with the age, it were appeared these rats were worth the experimental animal.

Aging↗
PubMed1999

[Changes in Bruch's membrane in experimental hypercholesteremia in rats].

PURPOSE: We investigated the effect of high cholesterol diet for the aging changes in Bruch's membrane of rats. METHODS: After feeding a 4% cholesterol diet for 15 weeks to three young rats 3 months old and four aged rats 23 months old, we observed the morphological changes of Bruch's membrane by electron microscopy, and made a comparison with rats fed an ordinary diet. RESULTS: In one young rat fed a high-cholesterol diet, the endothelial basement membrane of the choriocapillaris formed multiple folds separated from the plasma membrane of the endothelium and showed lamellar thickening and crack in some areas. The elastic fiber layer in Bruch's membrane disappeared partly and some new microfibrils appeared. In one aged rat fed a high-cholesterol diet, the endothelial basement membrane of the choriocapillaris showed more lamellar thickening with lumps in some parts. Compared with rats fed an ordinary diet, rats fed a high-cholesterol diet showed thickening of the basement membrane and the changes were more severe. CONCLUSIONS: Our data indicated that high-cholesterol diet might promote age-related changes of Bruch's membrane.

Aging↗
PubMed1999

[Exercise-induced acute renal failure associated with renal vasoconstriction].

Exercise-induced acute renal failure without rhabdomyolysis is not a rare condition. We experienced 6 cases (5 men and a woman) during last the 8 years. All cases complained of severe loin pain and nausea after mild to moderate exercises (for example, a track race in an athletic meeting). The elevation of serum and urinary myoglobin was undetected. In 4 of 5 patients with abdominal CT, renal patchy vasoconstriction (wedge-shaped low-density lesion) was observed. This was diagnosed as exercise-induced acute renal failure with loin pain (serum creatinine levels: 1.7-8.6 mg/dl). The renal function in 5 of the 6 cases normalized in about three weeks by fluid replacement therapy and hemodialysis support, which one patient received for 3 days. One patient required a long time for improvement of renal function and renal insufficiency persisted (serum creatinine 1.8 mg/dl). In 2 patients, the concentration of serum uric acid became very low after the recovery of renal function. These two patients were diagnosed as an isolated hyperuricosuric hypouricemia. More than half of the 6 patients had previously experienced the same episodes (loin pain and nausea) after exercise. Exercise-induced acute renal failure, probably due to renal patchy vasoconstriction, seems to be not a rare disease. The etiology of renal patchy vasoconstriction after exercises remains to be elucidated. The occurrence of acute renal failure must be taken into consideration when the youngster, especially with renal hypouricemia, complains of severe loin pain and nausea after exercise such as a track race.

Acute Kidney Injury↗
PubMed1999

Fractional myocardial flow reserve (FFRmyo) after coronary intervention as a predictor of chronic restenosis.

The angiographic assessment of coronary stenosis has many limitations, especially after coronary intervention. To determine the physiologic significance of such lesions, we measured the mean translesional pressure gradients at rest (P1), those during hyperemia induced by intracoronary administration of papaverine (12 mg in the left and 8 mg in the right coronary artery) (P2), and fractional myocardial flow reserve (FFRmyo) which is derived from the ratio of the mean distal coronary pressure and aortic pressure during hyperemia. Our objective was to determine the relations among P1, P2, and FFRmyo and restenosis as potential predictors of chronic restenosis. The grouped study consisted of 32 patients with ischemic heart disease scheduled to undergo intervention. The distal coronary pressure was measured using a 0.014 inch pressure monitoring wire (Pressure Guide, Radi Medical Systems, Uppsala, Sweden). The guidewire was advanced through the lesional segment. The mean percent diameter stenosis (%DS) was 67.9 +/- 13.3% before intervention and 22.9 +/- 15.3% after intervention. The mean P2 (9.9 +/- 5.3 mmHg) was significantly higher than the mean P1 (4.5 +/- 3.6 mmHg; p < 0.0001). There was no correlation of P1, P2 or FFRmyo with the %DS after intervention. Follow-up angiography (after 6 months) performed on all patients revealed restenosis (%DS > or =50%) in four patients (12.5%). There was no correlation between P1 and the %DS at the follow-up angiography, but the relation between P2, FFRmyo and the %DS at the follow-up angiography was significant (r = 0.599, p < 0.01; r = 0.703, p < 0.0001, respectively). As a measurement of P2, FFRmyo is useful for the determination of the endpoint of intervention in consideration of prevention of restenosis. A new endpoint may be established after further evaluation in a greater number of patients.

Aged↗
PubMed1998

Molecular genetic and immunohistochemical study of autosomal recessive Alport's syndrome.

A DNA analysis of autosomal type IV collagen alpha3 and alpha4 chain genes (COL4A3 and COL4A4) and an immunohistochemical study of type IV collagen alpha1 to alpha6 chains were performed in an inbred family with autosomal recessive Alport's syndrome (AS). A linkage study using polymorphic markers around the COL4A3/COL4A4 genes clearly differentiated the affected patients from healthy individuals. These patients were homozygous for all markers analyzed, whereas their parents were heterozygotes. Because of the large size of both the genes and the heterogeneous range of the mutations of these genes, linkage analysis by using highly polymorphic markers is still the method of choice in genetic counseling for autosomal recessive AS, as well as for the X-linked form. Although the distribution of alpha1 and alpha2 chains in the index patient and her affected sister were normal, the alpha3 and alpha4 chains were completely defective in the renal basement membrane (BM). The alpha5 chain could be found in Bowman's capsular basement membrane (BCBM) but not in the glomerular basement membrane (GBM). In addition, our study showed, for the first time, that the alpha6 chain in BCBM is spared in this form of AS. This abnormal pattern of type IV collagen could be a useful tool for differentiation of the autosomal recessive type from the X-linked type of AS.

Adolescent↗
PubMed1994

[Histopathological study of trabecular meshwork after trabeculotomy in monkeys].

Trabeculotomy is a commonly indicated surgical procedure for primary open angle glaucoma and congenital glaucoma. In order to clarify the mechanisms of lowering the intraocular pressure (IOP) following the intervention, we performed this procedure in monkey eyes, and did postoperative histopathological examinations using light microscopy, and scanning and transmission electronmicroscopy for trabecular mesh work specimens incised at various time intervals up to one year after operation. Immediately after the operation, a direct communication was seen between the Schlemm's canal and the anterior chamber. Subsequently, the repairing process of trabecular tissue occurred initially in the corneoscleral and endothelial meshwork and finally in the uveal meshwork. At one year after operation the chamber angle was almost completely repaired by newly-formed trabecular tissue which was identical to the normal trabecular tissue. There was no direct communication between the Schlemm's canal and anterior chamber at that time. These results suggest that the decreased resistance for the aqueous outflow might be caused by direct communication between the Schlemm's canal and anterior chamber at an early postoperative stage, and the repairing process of the endothelial meshwork increases the resistance of aqueous outflow.

Animals↗
PubMed1993

Sequential observation of mitochondrial distribution in mouse oocytes and embryos.

OBJECTIVE: The purpose of this study was to elucidate changes in the distribution of mitochondria through the cell cycle. MATERIALS AND METHODS: Mouse oocytes and embryos were recovered sequentially from mice and stained with the vital fluorescent mitochondrial stain rhodamine 123. Mitochondrial staining pattern were classified into three types: aggregation (Ag), homogeneous (H), and perinuclear accumulation (PA). RESULTS: Sequential observations revealed that mitochondria of oocytes and embryos grown in vivo translocated in the cytoplasm during the cell cycle, showing the H pattern before human chorionic gonadotropin (hCG) administration, the PA pattern 8-9 hr post-hCG, the H pattern again 10-14 hr post-hCG, and the PA pattern again 24 and 31-32 hr post-hCG following fertilization. In the two-cell stage, the Ag pattern was shown 35 hr post-hCG, the H pattern was observed 40 hr post-hCG, and the PA pattern was found 48 hr post-hCG. In the embryos cultured in vitro and showing developmental block, mitochondrial translocation was shown to be inhibited after they aggregated in the early two-cell stage (35 hr post-hCG). Moreover, the translocation of mitochondria was restored by the addition of superoxide dismutase or thioredoxin to the culture medium. Both of these enzymes have already been shown to have the ability to overcome developmental block. CONCLUSION: The present study revealed that mitochondria translocated in the cell cycle and suggested that there is a close relationship between mitochondrial translocation and developmental arrest.

Animals↗
PubMed1993

[Inhibitory effect of prior panretinal photocoagulation on experimental iris neovascularization].

We could produce iris neovascularization experimentally in rhesus monkey eyes, by occlusion of the major retinal vessels of the retina and persistent ocular hypotony. We confirmed that panretinal photocoagulation inhibits development of iris neovascularization. We evaluated the effect of panretinal photocoagulation one month before occlusion of major retinal vessels with secondary iris neovascularization in 3 monkey eyes. Rubeosis iridis appeared on day 5 and disappeared on day 14 after retinal vessel occlusion. Histologically, the newly formed vessels near the iris surface showed fenestrations and protruded into the anterior chamber. The endothelial cells were flat and similar to matured vessels. These findings were in sharp contrast to our previous experiments with panretinal photocoagulation after rubeosis iridis became manifest. The findings also showed that retinal scarring by preceding panretinal photocoagulation did not completely inhibit the iris neovascularization.

Animals↗
PubMed1992

Pregnancy achieved by transferring blastocysts into endometrial stroma in mice.

To prevent the extra-uterine discharge of transferred embryos, we directly inserted mouse embryos into the endometrial stroma (intra-endometrial embryo transfer). A 27G injection needle was inserted near the utero-tubal junction into the endometrial stroma. After removal of the needle, a glass micropipette was inserted and one embryo was transferred with a very small amount of culture medium. To determine the feasibility of this method, the uterine lumen was flushed with phosphate-buffered saline from the tubal ends immediately after transferring blastocysts into pseudopregnant mice on day 2 and day 4. The rates of recovery of embryos from the uterine lumen were 5.0% (1/20; day 4) and 15.0% (3/20; day 2). These results suggest that a high rate of intra-endometrial embryo transfer is possible. The embryonic viability rates (number of viable grown fetuses/number of blastocysts transferred) of this method were 50.0% (28/56; day 4) and 25.0% (5/20; day 2). Living offspring were delivered from both recipients which had received embryos on day 2 and day 4 of pseudopregnancy. In human in-vitro fertilization and embryo transfer, attempts have also been made to immobilize the embryos, and this method might be clinically applicable. Moreover, this method will be a good in-vivo model for studies on the mechanism of implantation.

Abortion, Veterinary↗
PubMed1992

[Morphological study of rubeosis iridis induced in animal eyes].

Rubeosis iridis was produced experimentally in rhesus monkey eyes, by means of occlusion of the major retinal vessels of the retina and persistent ocular hypotony. Clinically, rubeosis iridis was recognized 5 days after the procedure. Histopathologically, these vessels developed anteriorly to the iris surface and endothelial fenestrations showed evidence of iris neovascularization. Endothelial cells of the vessels projected toward the internal lumen and showed immaturity. Newly formed vessels originated from the stromal vessels in the iris. This method is an effective experimental model for the induction of rubeosis iridis.

Animals↗
PubMed1992

[Effect of pan-retinal photocoagulation in iris neovascularization].

The authors were able to produce experimental rubeosis iridis in the rhesus monkey's eye on 5 days following occlusion of the major retinal vessels and persistent ocular hypotony. Histopathological examination revealed true neovascularization. This experiment attempted to see whether laser pan-retinal photocoagulation plays an inhibiting effect on the occurrence of rubeosis iridis or not. We first performed laser pan-retinal photocoagulation, and at the same time performed occlusion of the major retinal vessels and persistent hypotony to aid for rubeosis iridis. Clinically, rubeosis iridis appeared within 5 days. At 14 days, histological examination revealed vessels on the surface of the iris following pan-retinal photocoagulation treatment were covered by fibroblast and melanocyte, and their endothelial cells showed no fenestrations. This means that clinical rubeosis iridis is not true neovascularization, but dilatation of the iris vessels. Thus, it was confirmed that pan-retinal photocoagulation inhibits development of iris neovascularization.

Animals↗
PubMed1991

[A morphological study of experimental intravitreal proliferative tissues].

Experimental tractional retinal detachments in rabbits' eyes was produced several weeks following aspiration of vitreous gels through a posterior small window of the eye wall. Histological examination showed that intravitreal proliferative tissues contained many fibroblasts, derived from the optic disc a small amount of migrated RPE, macrophages and other cells associated with proliferative tissues, Glial cells also grew especially at the epi-retina, causing shrinkage of the sensory retina. Vitreous neovascularization deriving from the retinal vessels was also found in these proliferative tissues. Our experimental data indicated that the extent of proliferative tissues mainly depend upon the amount of vitreous loss and vitreous hemorrhage, and the duration of retinal detachment. This experiment may be useful as an animal model of vitreous neovascularization.

Animals↗